Periodontal infections, which affect a large portion of the population, are responsible for the loss of teeth in adults and likely contribute to systemic disease. The most common method of controlling periodontal infections is my daily mechanical plaque removal. However, many individuals, due to lack of ability of poor compliance, do not remove sufficient dental plaque to adequately control periodontal infections. Hence, there is need for chemotherapeutic agents as adjuncts to personal oral hygiene to reduce plaque and gingivitis. Present anti-gingivitis agents suffer from one or more serious drawback including staining of teeth, objectionable taste, or modest clinical effects which limit their efficacy or usefulness. We have developed a series of salicyanilides which are antimicrobial, anti-inflammatory, highly lipophilic, substantive, and have a wide safety margin. One of these, a 5-acylsalicylanilide, has been shown to inhibit plaque in humans to an extent comparable to chlorhexidine, and also to reduce gingivitis in the absence of staining or adverse taste. In the Phase I study, a single agent, Trifluorosal, identified from a field of 22 candidate 5-alkylsulfonyl salicylanilides, exhibited potent antimicrobial and anti-inflammatory activity. It also has high lipophilicity, making it well suited for topical use, since it is substantive; absorbed and released in a locally active form; and has a low potential for systemic absorption leading to a wide margin of safety. It has also been shown to be non-toxic in a single high dose acute toxicity test. In the Phase II study this agent, Trifluorosal, will be employed to (1) develop optimal vehicles of delivery; (2) distinguish relative importance of biologic properties; (3) demonstrate efficacy in vivo in animals; and (4) provide safety data to support feasibility of use in man. Findings from this Phase II study could result in a safe and effective drug specifically designed for oral use capable of exerting control over oral diseases. Proposed commercial applications: Drugs developed in this project are intended for use in mouth rinses, toothpastes, or professionally applied gels to be used for the control of gingivitis and periodontal diseases. These may be either ethical pharmaceuticals or OTC oral hygiene products.